Zardavas Dimitrios, Piccart-Gebhart Martine
Breast International Group (BIG), Brussels 100, Belgium.
Medicine Department, Institut Jules Bordet, Université Libre de Bruxelles, Brussels 100, Belgium.
Cancer Biol Med. 2016 Jun;13(2):226-35. doi: 10.20892/j.issn.2095-3941.2015.0099.
The implementation of molecular profiling technologies in oncology deepens our knowledge for the molecular landscapes of cancer diagnoses, identifying aberrations that could be linked with specific therapeutic vulnerabilities. In particular, there is an increasing list of molecularly targeted anticancer agents undergoing clinical development that aim to block specific molecular aberrations. This leads to a paradigm shift, with an increasing list of specific aberrations dictating the treatment of patients with cancer. This paradigm shift impacts the field of clinical trials, since the classical approach of having clinico-pathological disease characteristics dictating the patients' enrolment in oncology trials shifts towards the implementation of molecular profiling as pre-screening step. In order to facilitate the successful clinical development of these new anticancer drugs within specific molecular niches of cancer diagnoses, there have been developed new, innovative trial designs that could be classified as follows: i) longitudinal cohort studies that implement (or not) "nested" downstream trials, 2) studies that assess the clinical utility of molecular profiling, 3) "master" protocol trials, iv) "basket" trials, v) trials following an adaptive design. In the present article, we review these innovative study designs, providing representative examples from each category and we discuss the challenges that still need to be addressed in this era of new generation oncology trials implementing molecular profiling. Emphasis is put on the field of breast cancer clinical trials.
分子谱分析技术在肿瘤学中的应用加深了我们对癌症诊断分子格局的认识，识别出可能与特定治疗易感性相关的畸变。特别是，越来越多的分子靶向抗癌药物正在进行临床开发，旨在阻断特定的分子畸变。这导致了一种范式转变，越来越多的特定畸变决定了癌症患者的治疗。这种范式转变影响了临床试验领域，因为传统的根据临床病理疾病特征决定患者纳入肿瘤学试验的方法正转向将分子谱分析作为预筛选步骤来实施。为了促进这些新抗癌药物在癌症诊断的特定分子领域内成功进行临床开发，已经开发了新的、创新的试验设计，可分类如下：i）实施（或不实施）“嵌套”下游试验的纵向队列研究，ii）评估分子谱分析临床效用的研究，iii）“主”方案试验，iv）“篮子”试验，v）采用适应性设计的试验。在本文中，我们回顾了这些创新研究设计，提供了每个类别的代表性例子，并讨论了在实施分子谱分析的新一代肿瘤学试验时代仍需解决的挑战。重点放在乳腺癌临床试验领域。
